Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization |
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Authors: | Vitaly A Kushnir Yao Yu David H Barad Andrea Weghofer Eric Himaya Ho-Joon Lee Yan-Guang Wu Aya Shohat-Tal Emanuela Lazzaroni-Tealdi Norbert Gleicher |
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Institution: | 1. Center for Human Reproduction, New York, New York, United States of America.; 2. Foundation for Reproductive Medicine, New York, New York, United States of America.; 3. Department of Obstetrics and Gynecology, University of Vienna School of Medicine, Vienna, Austria.; 4. Gatineau Hospital, McGill University, Quebec, Canada.; Michigan State University, United States of America, |
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Abstract: | ContextMutations of the fragile X mental retardation 1 (FMR1) gene are associated with distinct ovarian aging patterns.ObjectiveTo confirm in human in vitro fertilization (IVF) that FMR1 affects outcomes, and to determine whether this reflects differences in ovarian aging between FMR1 mutations, egg/embryo quality or an effect on implantation.Design, Setting, PatientsIVF outcomes were investigated in a private infertility center in reference to patients'' FMR1 mutations based on a normal range of CGGn = 26–34 and sub-genotypes high (CGGn>34) and low (CGG<26). The study included 3 distinct sections and study populations: (i) A generalized mixed-effects model of morphology (777 embryos, 168 IVF cycles, 125 infertile women at all ages) investigated whether embryo quality is associated with FMR1; (ii) 1041 embryos in 149 IVF cycles in presumed fertile women assessed whether the FMR1 gene is associated with aneuploidy; (iii) 352 infertile patients (< age 38; in 1st IVF cycles) and 179 donor-recipient cycles, assessed whether the FMR1 gene affects IVF pregnancy chances via oocyte/embryo quality or non-oocyte maternal factors.InterventionsStandardized IVF protocols.Main Outcome MeasuresMorphologic embryo quality, ploidy and pregnancy rates.Results(i) Embryo morphology was reduced in presence of a low FMR1 allele (P = 0.032). In absence of a low allele, the odds ratio (OR) of chance of good (vs. fair/poor) embryos was 1.637. (ii) FMR1 was not associated with aneuploidy, though aneuploidy increased with female age. (iii) Recipient pregnancy rates were neither associated with donor age or donor FMR1. In absence of a low FMR1 allele, OR of clinical pregnancy (vs. chemical or no pregnancy) was 2.244 in middle-aged infertility patients.ConclusionsA low FMR1 allele (CGG<26) is associated with significantly poorer morphologic embryo quality and pregnancy chance. As women age, low FMR1 alleles affect IVF pregnancy chances by reducing egg/embryo quality by mechanisms other than embryo aneuploidy. |
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